Clostridioides difficile infection (CDI) is an urgent public health threat with limited preventative options. In this work, we developed a messenger RNA (mRNA)–lipid nanoparticle (LNP) vaccine targeting C. difficile toxins and virulence factors. This multivalent vaccine elicited robust and long-lived systemic and mucosal antigen-specific humoral and cellular immune responses across animal models, independent of changes to the intestinal microbiota. Vaccination protected mice from lethal CDI in both primary and recurrent infection models, and inclusion of non-toxin cellular and spore antigens improved decolonization of toxigenic C. difficile from the gastrointestinal tract. Our studies demonstrate mRNA-LNP vaccine technology as a promising platform for the development of novel C. difficile therapeutics with potential for limiting acute disease and promoting bacterial decolonization.

中文翻译：

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多价 mRNA-LNP 疫苗可预防艰难梭菌感染


艰难梭菌感染 （CDI） 是一种紧迫的公共卫生威胁，预防选择有限。在这项工作中，我们开发了一种针对艰难梭菌毒素和毒力因子的信使 RNA （mRNA）-脂质纳米颗粒 （LNP） 疫苗。这种多价疫苗在动物模型中引起了强大且长寿命的全身和粘膜抗原特异性体液和细胞免疫反应，与肠道微生物群的变化无关。在原发性和复发性感染模型中，疫苗接种可保护小鼠免受致命的 CDI 感染，并且包含非毒素细胞和孢子抗原改善了产毒艰难梭菌从胃肠道的去定植。我们的研究表明，mRNA-LNP 疫苗技术是开发新型艰难梭菌疗法的一个有前途的平台，具有限制急性疾病和促进细菌去定植的潜力。